![]() examined dimeric inhibin A as yet another marker to be added to the second trimester screening profile and this was later dubbed the ‘quadruple screen’. ![]() Looking across all maternal ages, the triple screen detection rate for Down syndrome in the second trimester was 60% with a false-positive rate of 5%, essentially doubling the detection rate from age alone. The mean for the analytes β-hCG, AFP and uE 3 in a second trimester pregnancy affected with Down syndrome were 2.1, 0.7 and 0.7 MoM respectively. Overall, the mean levels of these analytes were expressed as a multiple of the expected value for gestational age based on a log–linear regression in the controls, multiples of the median (MoM). combined the maternal serum markers of β-hCG, α-fetoprotein (AFP) and uE 3 with maternal age in the ‘triple screen’ in 1988. After observations with MSAFP, altered maternal serum levels in affected pregnancies were observed in other analytes: free β-human chorionic gonadotropin (β-hCG), inhibin A and unconjugated estriol (uE 3). This led to the first protocols for fetal aneuploidy screening in the general population across all maternal ages. This study modeled a mathematical algorithm that combined maternal age and MSAFP in the second trimester to detect 40% of cases of Down syndrome with a false-positive rate of 6.8%. Simultaneously, MSAFP was suggested by Cuckle as a screening test for Down syndrome in the general population. in 1984 that maternal serum α-fetoprotein (MSAFP) in the second trimester was significantly lower in a woman with a trisomy 18 fetus. The first recommendation for prenatal aneuploidy screening in the general population stemmed from the observation by Merkatz et al. Maternal age was a poor screening test in isolation because it only identified 25–30% of fetal aneuploidy. With the advent of cytogenetic analysis on cultured amniocytes in the 1970s, all women aged >36 years were offered amniocentesis to diagnose potential fetal aneuploidy. Dr Lionel Penrose was the first to recognize this concept in the 1930s when he observed that there was a significant association between increasing maternal age and birth of a Down syndrome child. Prior to the 1980s, the primary method to identify women at risk for aneuploidy was based on the concept of increased risk with advanced maternal age.
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